The overall goal of this project is to determine how iron homeostasis and C1 metabolism are coordinated in Methylobacterium extorquens AM1. Iron has become an interesting focal point for research in M. extorquens AM1 because of three initial discoveries I made. First, microarray data show increased iron uptake gene expression when M. extorquens AM1 is grown on C1 substrates suggesting an increased requirement for iron. Second, gel retardation assays and microarray data suggest QscR, a regulator of the serine cycle and obligate part of C1 metabolism, is also a global activator of iron uptake. And third, genomic studies suggest there are multiple differences in the components required for iron homeostasis between M. extorquens AM1 and the paradigm used for iron homeostasis studies, Escherichia coli. The Specific Aims of this proposal are: 1) to elucidate the key components of iron regulation in M. extorquens AM1 and the physiological role of iron in C1 metabolism and 2) to determine the role of QscR in iron homeostasis and the cross-regulation that occurs between iron homeostasis and C1 metabolism in M. extorquens AM1. [unreadable] [unreadable] [unreadable]